Blockade of IGF-IR exerts anticancer effects in hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and is characterized by a high degree of malignancy and a low survival rate. Most HCCs express insulin-like growth factors and their receptors (IGF-IR), which mediate signaling, promote survival and invasion, and prevent apoptosis. Thus, they may be potential targets for the treatment of HCCs. In the present study, the potential therapeutic effect of Tyrphostin AG1024 in HCC was examined. After treatment with various concentrations of AG1024 (one selective inhibitor of IGF-IR), AG1024 not only dose-dependently inhibited the proliferation of HCC cells and induced apoptosis, but also markedly inhibited invasion ability. Expression of proteins detected by Western blot analysis revealed that AG1024 dose-dependently increased the expression of cytochrome C, while procaspase-3 and phospho-ERK were down-regulated. Thus, IGF-IR inhibition may be a promising novel approach to the treatment of HCC.